The influence of mitochondrial dynamics on mitochondrial genome stability

Curr Genet. 2018 Feb;64(1):199-214. doi: 10.1007/s00294-017-0717-4. Epub 2017 Jun 1.

Abstract

Mitochondria are dynamic organelles that fuse and divide. These changes alter the number and distribution of mitochondrial structures throughout the cell in response to developmental and metabolic cues. We have demonstrated that mitochondrial fission is essential to the maintenance of mitochondrial DNA (mtDNA) under changing metabolic conditions in wild-type Saccharomyces cerevisiae. While increased loss of mtDNA integrity has been demonstrated for dnm1-∆ fission mutants after growth in a non-fermentable carbon source, we demonstrate that growth of yeast in different carbon sources affects the frequency of mtDNA loss, even when the carbon sources are fermentable. In addition, we demonstrate that the impact of fission on mtDNA maintenance during growth in different carbon sources is neither mediated by retrograde signaling nor mitophagy. Instead, we demonstrate that mitochondrial distribution and mtDNA maintenance phenotypes conferred by loss of Dnm1p are suppressed by the loss of Sod2p, the mitochondrial matrix superoxide dismutase.

Keywords: Genome instability; Mitochondria; Mitochondrial DNA (mtDNA); Mitochondrial dynamics; Mitochondrial genome.

MeSH terms

  • Carbon / metabolism
  • Cell Respiration / genetics
  • DNA Breaks, Double-Stranded
  • DNA Repair
  • DNA, Mitochondrial
  • GTP Phosphohydrolases / genetics
  • GTP Phosphohydrolases / metabolism
  • Gene Deletion
  • Genome, Mitochondrial*
  • Genomic Instability*
  • Mitochondria / genetics*
  • Mitochondria / metabolism*
  • Mitochondrial Dynamics*
  • Mitochondrial Membranes / metabolism
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism
  • Mutation
  • Raffinose / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Sequence Deletion

Substances

  • DNA, Mitochondrial
  • Mitochondrial Proteins
  • Saccharomyces cerevisiae Proteins
  • Carbon
  • GTP Phosphohydrolases
  • DNM1 protein, S cerevisiae
  • Raffinose